In this renewal the Berkeley PGA proposes to continue to accelerate heart, lung and blood (HL&B) research through facilitating the application of comparative genomics resources and approaches to the identification of biomedically relevant features in the human genome. Our production efforts will focus on DNA sequence generation, and the development of user friendly analysis tools and databases. In addition, through education programs and biological demonstration projects by the Berkeley PGA we will encourage biomedical investigators to exploit the Berkeley PGA's genomic resources to achieve those goals. These activities will include: 1) sequencing for HL&B investigators biomedically relevant regions in the genomes of organisms not being sequenced by the public sequencing efforts, 2) the development of user friendly comparative genomic tools and databases focused on aiding biomedical investigators, 3) a multifaceted education program targeted at training HL&B researchers in the use of genomic informatics, 4) "high-throughput" in vivo assessment of the function of sequences in the human genome identified by cross-species sequence comparisons in genetically engineered mice and Ciona intestinalis and 5) clinical resequencing projects to examine a large set of candidate genes potentially causing sporadic HI&B disorders.